My earlier work in the isolated perfused rat mesenteric arteries indicates that glucose, adenine nucleotides and glucose metabolites may play an important role in adrenergic transmission by maintaining an intraneuronal Na ion and K ion concentration. Further preliminary work which shows that glucose deprivation increases vascular tone in the rabbit but not in the rat suggests that glucose (or metabolites) may also be involved in the regulation of vascular tone, and this effect appears to be species dependent. The proposed study intends to define the role of glucose, adenine nucleotides, and metabolites as possible determinants of the regulation of vascular tone and their interaction with the adrenergic nervous system in various vascular beds of different animal species. In the isolated perfused mesenteric, renal and splenic vasculature of rabbit, rat and cat, I plan to investigate the effects of various sugars, adenine nucleotides and glucose metabolites on the vascular tone and its responsiveness to adrenergic stimuli. Changes in the later will be related to the ouput of adrenergic transmitter evoked by nerve stimulation and other adrenergic mechanisms such as synthesis, storage and inactivation of the adrenergic transmitter. The relationship of locally generated glucose metabolites to adrenergic neuroeffector events will be investigated after inhibition of glucose metabolism. I shall also attempt to define the effect of glucose and its metabolites on the vascular tone and vascular reactivity to adrenergic stimuli as modified by changes in the electrolyte composition of the medium. The definition of altered vascular tone and its reactivity to adrenergic stimuli and various adrenergic mechanisms may provide valuable information about some vascular diseases and neurogenic disorders such as diabetic neuropathy.